Project description:Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to metabolic dysfunction-associated steatohepatitis (MASH) and is a major cause of liver cirrhosis. Although liver inflammation is the hallmark feature of MASH vs MAFLD, the involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study. Patients have been histologically stratified and further characterized by liver bulk RNA-Seq. Peripheral immune cells from patients and control blood samples have been comprehensively profiled using bulk and single RNA-Seq. Results: 22 patients with fibrosis stage less then F3 have been histologically stratified into patients with low, medium and high disease activity score (NAS). In contrast to fibrosis, NAS group correlated with non-invasive imaging readouts and blood biomarkers of liver damage and inflammation (ALT, AST). Prevalence of type 2 diabetes and obesity was increased with NAS stage. Bulk RNA-seq profiling of patient liver biopsies revealed gene signatures that were positively and negatively associated with NAS. Known marker genes for liver fibrosis where up-regulated on RNA level. Blood bulk RNA-sequencing showed only moderate differences in patients versus healthy controls. In contrast, single cell analysis of white blood cells revealed multiple alterations of immune (sub-) populations including increased abundance of immature B-cells and myeloid suppressor cells in MAFLD/MASH patients as well as disease-association of neutrophil sub-populations.
Project description:Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to steatohepatitis (MASH) and is a major cause of liver cirrhosis. In the early disease stage, liver inflammation is absent. However, the early involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study. Patients have been histologically stratified and characterized by liver bulk RNA-Seq.
Project description:Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to steatohepatitis (MASH) and is a major cause of liver cirrhosis. In the early disease stage, liver inflammation is absent. However, the early involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study characterized by White Blood bulk RNA-Seq.
Project description:Surgery still remains the mainstay of treatment for localized colorectal cancer. However, nearly 30% of patients with localized colorectal cancer (stage II and stage III) will present with recurrence. Tumor progression is mediated by both intrinsic genetic changes and by extrinsic epigenetic and host environmental factors, including interactions with the immune system. Several studies demonstrated that tumor infiltrating memory T-cells and type, density and location of infiltrating T cells are better predictors of disease-free survival in patients with CRC compared to the standard TNM staging. These data suggest that tumor invasion and progression are more accurately predicted by immune response in the primary tumor. In addition, mismatch repair (MMR)-deficient tumors are characterized a priori by a higher frequency of tumor infiltrating lymphocytes and are associated with significantly improved prognosis. Recently, Stotz et al showed that the preoperative lymphocyte to monocyte ratio in peripheral blood samples predicts clinical outcome in patients with stage III colon cancer. So far there is no comprehensive analysis of the immune-landscape in CRC.
The aim of the current project is to identify a comprehensive panel of immunomarkers in localized colorectal cancer (stage II and stage III) applicable for the detection of patients at high risk of recurrence. For the first time, specific tumor-infiltrating immune cells, mismatch repair protein expression in tumor tissue and preoperative blood based inflammatory markers from routine blood counts in corresponding peripheral blood samples and known clinicopathological features will be correlated with outcome in 300 localized CRC patients.
Project description:MAFLD is a heterogenous spectrum disorder affecting 20% of the population. Inflammatory processes contribute to various stages of MAFLD and thought to instigate hepatic fibrosis. For this reason, targeting inflammation has been heavily nominated as an approach to mitigating liver fibrosis. Lipopolysaccharide binding protein is a secreted protein that plays an established role in innate immune responses. In a murine model of MAFLD, we used a liver-specific deletion of LBP model to study its role in hepatic inflammation. Single nucleus RNA-seq were applied to investigate the role of LBP in hepatic cell composition.